Product Name: PLGLAG
Sequence: Pro-Leu-Gly-Leu-Ala-Gly
Purity: 98%
Form: White to off-white Solid
Storage : Sealed storage, away from moisture
CAS.NO.: 726172-45-8
SMILES: C[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1
CHEMICAl FORMULA: C24H42N6O7
IUPACNAME: 2-[[(2S)-2-[[(2S)-4-methyl-2-[[2-[[(2S)-4-methyl-2-[[(2S)-pyrrolidine-2-carbonyl]amino]pentanoyl]amino]acetyl]amino]pentanoyl]amino]propanoyl]amino]acetic acid
INCHIKEY: CTVSTBZSGZTUJX-XSLAGTTESA-N
INCHI: InChI=1S/C24H42N6O7/c1-13(2)9-17(30-23(36)16-7-6-8-25-16)22(35)26-11-19(31)29-18(10-14(3)4)24(37)28-15(5)21(34)27-12-20(32)33/h13-18,25H,6-12H2,1-5H3,(H,26,35)(H,27,34)(H,28,37)(H,29,31)(H,30,36)(H,32,33)/t15-,16-,17-,18-/m0/s1
Molarmass: 526.63
Application: PLGLAG is a protease-cleavable peptide linker commonly used in activatable cell-penetrating peptide (ACPP) systems for cancer research. This short sequence can be incorporated between a cell-penetrating domain and an inhibitory or masking domain, enabling protease-responsive activation in tumor-associated microenvironments. Because matrix metalloproteinases and other cancer-related proteases are often elevated in invasive tumors, PLGLAG-based linkers are useful for studying targeted cellular uptake, tumor imaging, and conditional peptide delivery. PLGLAG is widely applied in ACPP design, oncology research, protease activity assays, tumor-targeted delivery platforms, and development of activatable diagnostic or therapeutic peptide systems.
Current Research: PLGLAG is a short protease-cleavable peptide sequence widely used as a linker in activatable cell-penetrating peptides, also known as ACPPs. ACPPs are engineered peptide systems designed to remain relatively inactive until they encounter a specific protease activity in the target microenvironment. In many cancer research applications, PLGLAG functions as the enzyme-sensitive linker between a cell-penetrating peptide domain and an inhibitory or masking domain. Once cleaved by tumor-associated proteases, the cell-penetrating portion becomes unmasked and can promote cellular uptake of an attached imaging probe, drug payload, nanoparticle, or molecular cargo. A major research application of PLGLAG is matrix metalloproteinase-responsive peptide design. Matrix metalloproteinases, or MMPs, are proteolytic enzymes involved in extracellular matrix remodeling, invasion, angiogenesis, inflammation, and tumor progression. Many tumors show increased MMP activity in the tumor microenvironment, especially in invasive fronts, stromal regions, and areas of active tissue remodeling. PLGLAG-containing constructs are used to study how protease activity can be converted into selective activation of a peptide-based delivery or imaging system. The core concept behind PLGLAG-based ACPPs is molecular masking. A typical ACPP contains a polycationic cell-penetrating peptide, a polyanionic inhibitory domain, and a protease-cleavable linker such as PLGLAG. Before cleavage, the polyanionic domain suppresses the interaction of the cationic cell-penetrating domain with cell membranes, reducing nonspecific uptake. After protease cleavage, the inhibitory segment separates from the cell-penetrating segment, allowing the activated peptide conjugate to bind cells and enter tissue more efficiently. This strategy is valuable in cancer research because it uses enzyme activity rather than receptor expression alone as the trigger for localization. PLGLAG is especially useful in tumor imaging research. When incorporated into fluorescent, radiolabeled, or nanoparticle-based ACPP systems, the linker can enable protease-activated accumulation of imaging signal in MMP-rich tumor tissues. Researchers may use PLGLAG-based probes to visualize tumor margins, invasive regions, metastatic lesions, or protease-active microenvironments. Imaging platforms may include fluorescence microscopy, near-infrared imaging, optical surgical guidance models, PET/SPECT-compatible systems, or multimodal nanoparticle probes, depending on the cargo attached to the peptide system. In drug delivery research, PLGLAG can be used to create protease-activated delivery systems. Payloads may include cytotoxic agents, photosensitizers, nucleic acids, peptide inhibitors, protein cargoes, or nanoparticle-encapsulated drugs. The goal is to reduce nonspecific uptake in normal tissues while increasing activation in protease-rich disease environments. PLGLAG-containing linkers may be evaluated in cell culture, tumor spheroids, extracellular matrix models, organoids, and animal tumor models to test activation, uptake, distribution, and functional payload release. Cancer invasion and metastasis research represent another important field. MMP activity is closely associated with extracellular matrix degradation and tumor cell invasion. PLGLAG-based sensors can help researchers map protease activity in invasive cancer models and distinguish protease-active regions from total tumor mass. These systems are useful for studying tumor-stroma interactions, fibroblast activation, angiogenesis, matrix remodeling, and inflammatory protease contributions to tumor progression. PLGLAG is also valuable in enzyme specificity studies. While it is commonly used in MMP-responsive systems, cleavage behavior depends on the exact peptide context, flanking residues, steric accessibility, linker presentation, and protease type. Researchers may compare PLGLAG with other protease-cleavable linkers such as PLGC(Me)AG, GPLGVRG, PVGLIG, Val-Cit, Phe-Lys, or cathepsin-sensitive sequences to define which linker gives the best activation profile for a specific biological model. Protease panels are often used to assess selectivity against MMP-2, MMP-9, MMP-14, cathepsins, elastase, thrombin, plasmin, and other enzymes. In chemical biology, PLGLAG supports the design of activatable probes. These probes translate protease cleavage into fluorescence activation, cellular uptake, cargo release, or signal amplification. Researchers may attach fluorophore-quencher pairs, FRET modules, cell-penetrating domains, biotin handles, or affinity tags to PLGLAG-containing sequences. After cleavage, changes in fluorescence, mobility, retention, or binding can be measured to quantify enzyme activity. PLGLAG may also be incorporated into biomaterial systems. Protease-sensitive hydrogels, coatings, scaffolds, and extracellular matrix mimics use cleavable peptide linkers to respond to cell-secreted enzymes. In cancer and inflammation research, PLGLAG-containing materials can be used to study cell invasion, matrix degradation, local release of bioactive molecules, and protease-dependent remodeling. Such materials are especially useful in 3D culture models where cells interact with a degradable matrix. Assay development with PLGLAG requires careful controls. Recommended controls include uncleavable linker analogs, scrambled linker sequences, protease-free conditions, heat-inactivated protease, broad-spectrum MMP inhibitors, selective MMP inhibitors, recombinant protease controls, enzyme dose-response testing, and LC-MS or HPLC confirmation of cleavage products. In cell-based systems, researchers should also include viability controls, uptake controls, and protease-expression validation. For ACPP studies, it is important to distinguish protease-dependent activation from nonspecific uptake. Controls should include a non-cleavable ACPP, a constitutively active cell-penetrating peptide, a masked non-cleavable peptide, and inhibitor-treated cells or tissues. Fluorescence uptake alone may not prove selective activation, so researchers often combine imaging with biochemical cleavage analysis and protease inhibition. Overall, PLGLAG is a practical protease-cleavable linker for activatable peptide systems. It supports ACPP design, MMP-responsive delivery, cancer imaging, tumor microenvironment research, enzyme-activated probes, protease-sensitive biomaterials, targeted cargo delivery, invasion assays, and development of peptide-based tools that convert tumor-associated protease activity into measurable or functional biological responses.
Get a Quote
LinkPeptide
